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Enteric Inhibitory Neurotransmission, Starting Down Under

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The Enteric Nervous System

Part of the book series: Advances in Experimental Medicine and Biology ((ANS,volume 891))

Abstract

The idea of an inhibitory innervation in the gut came from Geoff Burnstock’s group at the University of Melbourne in the 1960s. Being resistant to antagonists of norepinephrine and acetylcholine, enteric inhibitory neurotransmission became known as non-cholinergic, non-adrenergic (NANC) neurotransmission. ATP (or a closely related nucleotide) was proposed as the inhibitory neurotransmitter based on release of purines during nerve stimulation and similarities between responses to ATP and transmural nerve stimulation in several gut preparations. Apamin was found to block purinergic responses, providing evidence that small-conductance Ca2+-activated K+ (SK) channels were responsible for inhibitory junction potentials (IJPs). Actually the IJPs in GI muscles are composed of multiple components, and later studies discovered nitric oxide (NO) to be the other major mediator of NANC inhibitory neurotransmission. The purinergic component of enteric inhibitory neurotransmission is mediated by P2Y1 receptors, and this component is absent in P2Y1−/− mice. The criteria for a neurotransmitter are better met by β-nicotinamide adenine dinucleotide (β-NAD) or its immediate metabolite ADP-ribose (ADPR) than by ATP. The cells mediating post-junctional responses have been identified. In addition to smooth muscle cells, two classes of interstitial cells express receptors and effectors for NANC neurotransmitters and are electrically coupled to smooth muscle cells. This integrated structure has been named the SIP syncytium. Interstitial cells of Cajal are involved in transduction of cholinergic and nitrergic inputs to GI muscles, and PDGFRα+ cells mediate purinergic effects. This short symposium report summarizes major historical points of interest and some of the more recent findings related to enteric inhibitory neurotransmission.

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Acknowledgements

Support for this review was provided by P01 DK41315 and R01 DK091336.

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Authors and Affiliations

  1. Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV, 89511, USA

    Kenton M. Sanders

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  1. Kenton M. Sanders
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Correspondence to Kenton M. Sanders .

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Editors and Affiliations

  1. Discipline of Medicine, University of Adelaide, Adelaide, South Australia, Australia

    Stuart Brierley

  2. Department of Human Physiology, School of Medicine, Flinders University,, Adelaide, South Australia, Australia

    Marcello Costa

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Sanders, K.M. (2016). Enteric Inhibitory Neurotransmission, Starting Down Under. In: Brierley, S., Costa, M. (eds) The Enteric Nervous System. Advances in Experimental Medicine and Biology(), vol 891. Springer, Cham. https://doi.org/10.1007/978-3-319-27592-5_3

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